DOS in Biochemistry, University of Mysore, Manasagangothri, Mysore, India.
Free Radic Res. 2013 May;47(5):357-67. doi: 10.3109/10715762.2013.781595. Epub 2013 Apr 8.
In the present human health scenario, implication of oxidative stress in numerous pathologies including neurodegenerative, cardiovascular, liver, renal, pulmonary disorders, and cancer has gained attention. N-Acetylcysteine (NAC), a popular thiol antioxidant, has been clinically used to treat various pathophysiological disorders. However, NAC therapy is routine only in paracetamol intoxication and as a mucolytic agent. Over six decades, numerous studies involving NAC therapy have yielded inconsistent results, and this could be due to low bioavailability. In order to overcome the limitations of NAC, an amide derivative N-Acetylcysteine amide (NACA) has been synthesized to improve the lipophilicity, membrane permeability, and antioxidant property. Recent studies have demonstrated the blood-brain barrier permeability and therapeutic potentials of NACA in neurological disorders including Parkinson's disease, Alzheimer's disease, Multiple sclerosis, Tardive dyskinesia, and HIV-associated neurological disorders. In addition, NACA displays protective effect against pulmonary inflammation and antibiotic-induced apoptosis. Forthcoming research on the possible therapeutic properties of NACA and its generics in the management of pathologies associated with extracellular matrix degradation and oxidative stress-related inflammation is highly exiting. Superior bioavailability of NACA is likely to fulfill the promises of NAC as well as a molecule to improve the endurance and resident time of bioscaffolds and biomaterials. Till date, more than 800 reviews on NAC have been published. However, no comprehensive review is available on the therapeutic applications of NACA. Therefore, the current review would be the first to emphasize the therapeutic potentials of NACA and its derivatives.
在当前的人类健康状况下，氧化应激在包括神经退行性疾病、心血管疾病、肝脏疾病、肾脏疾病、肺部疾病和癌症在内的许多疾病中的作用引起了关注。N-乙酰半胱氨酸（NAC）作为一种常用的巯基抗氧化剂，已在临床上用于治疗各种病理生理紊乱。然而，NAC 疗法仅在对乙酰氨基酚中毒和作为黏液溶解剂时常规使用。六十多年来，涉及 NAC 治疗的大量研究得出了不一致的结果，这可能是由于其生物利用度低。为了克服 NAC 的局限性，已经合成了 N-乙酰半胱氨酸酰胺（NACA）的酰胺衍生物，以提高亲脂性、膜通透性和抗氧化性能。最近的研究表明，NACA 在包括帕金森病、阿尔茨海默病、多发性硬化症、迟发性运动障碍和 HIV 相关神经紊乱在内的神经紊乱中具有血脑屏障通透性和治疗潜力。此外，NACA 还显示出对肺部炎症和抗生素诱导的细胞凋亡的保护作用。关于 NACA 及其类似物在管理与细胞外基质降解和氧化应激相关炎症相关疾病方面的可能治疗特性的即将到来的研究非常令人兴奋。NACA 的较高生物利用度可能会实现 NAC 作为改善生物支架和生物材料的耐力和驻留时间的分子的承诺。迄今为止，已经发表了超过 800 篇关于 NAC 的评论。然而，尚无关于 NACA 治疗应用的综合评论。因此，本综述将是第一篇强调 NACA 及其衍生物治疗潜力的综述。
